Document Detail

Pathogenic autoreactive B cells are not negatively selected toward matrix protein collagen II.
MedLine Citation:
PMID:  21940677     Owner:  NLM     Status:  MEDLINE    
We have addressed the importance of B cell tolerance to collagen type II, a matrix protein, which is a target in rheumatoid arthritis (RA) and its mouse models. We generated a germline-encoded anti-collagen type II (CII) IgH replacement anti-C1 B cell mouse strain (ACB) to investigate how B cell tolerance to CII, a matrix protein, is subverted and to further understand pathogenesis of RA. Phenotypic analysis revealed that CII-specific B cells were surprisingly neither deleted nor anergized. Instead, they were readily detected in all lymphoid organs. Spontaneously produced autoantibodies could bind directly to cartilage surface without detectable pathology. However, exaggerated arthritis was seen after injection of anti-CII Abs specific for other epitopes. In addition, Abs from CII-specific hybridomas generated from ACB mice induced arthritis. Interestingly, IgH/L chain sequence data in B cell hybridomas revealed a lack of somatic mutations in autoreactive B cells. The ACB model provides the first possibility, to our knowledge, to study B cell tolerance to a matrix protein, and the observations made in the study could not be predicted from previous models. B cell-reactive epitopes on CII are largely shared between human RA and rodent CII-induced arthritis; this study, therefore, has important implications for further understanding of pathological processes in autoimmune diseases like RA.
Duojia Cao; Ia Khmaladze; Hongwei Jia; Estelle Bajtner; Kutty S Nandakumar; Thomas Blom; John A Mo; Rikard Holmdahl
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-09-21
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  187     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-10-20     Completed Date:  2012-01-23     Revised Date:  2012-11-06    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4451-8     Citation Subset:  AIM; IM    
Medical Inflammation Research, Lund University, Lund, Sweden.
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MeSH Terms
Arthritis, Experimental / immunology*,  metabolism,  pathology
Arthritis, Rheumatoid / immunology,  metabolism,  pathology
Autoantibodies / metabolism
B-Lymphocyte Subsets / immunology*,  metabolism,  pathology*
Binding Sites, Antibody
Collagen Type II / immunology*
Disease Models, Animal
Epitopes, B-Lymphocyte / immunology
Extracellular Matrix Proteins / immunology*,  metabolism
Gene Knock-In Techniques
Immune Tolerance*
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Spleen / cytology,  immunology
Reg. No./Substance:
0/Autoantibodies; 0/Collagen Type II; 0/Epitopes, B-Lymphocyte; 0/Extracellular Matrix Proteins
Erratum In:
J Immunol. 2012 Sep 15;189(6):3263

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